tbuckley/cabot-search huggingface dataset:
Abstract 1111: The status of Government-funded radiotherapy centres in Nigeria
Authors: Simeon C. Aruah, Runcie C. Chidebe, Tochukwu C. Orjiakor, Fatima Uba, Uchechukwu Shagaya, Charles Ugwanyi, Aisha A. Umar, Taofeeq Ige, Obinna C. Asogwa, Oiza T. Ahmadu, Musa Ali-Gombe, Alabi Adewumi, Vitalis C. Okwor, Mutiu A. Jimoh, Basheer Bello, Lucy O. Eriba, Yusuf A. Ahmed, Awwal Bisalla, Ukamaka Itanyi, Ramatallah A. Balogun, Suleiman Alabi, David Pistenmaa, Coleman C. Norman, Dosanjh Manjit
Journal: Cancer Research (2023)

Abstract PURPOSE: Access to radiotherapy (RT) is now one of the stark examples of global cancer inequities. Over 800,000 new cancer cases require potentially curative or palliative RT services in Africa, arguably less than 15% of these patients currently have access to this important service. For a population of over 200 million, Nigeria requires a minimum of 280 RT machines for the increasing number of cancer cases. Painfully the country has only 8 government-funded radiotherapy machines. This study aimed to evaluate the status of the eight (8) Government-funded RT centres in Nigeria regarding RT equipment, workforce and infrastructure to quantify their ability to deliver effective RT to their patients. METHODS: A survey addressing ten (10) critical areas was used to assess the eight (8) Government-funded RT centres in Nigeria. RESULTS: Unfortunately, 6 of the 8 centres (75%) surveyed have not treated patients with RT over the last 2 years because they do not have functioning teletherapy machines. Only 2 RT centres have the capability of treating patients using advanced RT techniques. There is no PET-CT scan in any of the Government-funded RTcentres. The workforce capacity and infrastructure across the 8 centres are limited. All of the centres lack residency training programmes for medical physicists and radiation therapy technologists (RTTs) resulting in very few well-trained staff. CONCLUSION: As the Nigeria government plans for the new National Cancer Control Plan, there is an urgent need to scale up access to radiotherapy by upgrading the RT equipment, workforce and infrastructure to meet the current needs of Nigerian cancer patients. While the shortfall is apparent from a variety of radiotherapy-capacity data bases, this detailed analysis provides essential information for an implementation plan involving solutions from within Nigeria and with global partners. Citation Format: Simeon C. Aruah, Runcie C. Chidebe, Tochukwu C. Orjiakor, Fatima Uba, Uchechukwu Shagaya, Charles Ugwanyi, Aisha A. Umar, Taofeeq Ige, Obinna C. Asogwa, Oiza T. Ahmadu, Musa Ali-Gombe, Alabi Adewumi, Vitalis C. Okwor, Mutiu A. Jimoh, Basheer Bello, Lucy O. Eriba, Yusuf A. Ahmed, Awwal Bisalla, Ukamaka Itanyi, Ramatallah A. Balogun, Suleiman Alabi, David Pistenmaa, Coleman C. Norman, Dosanjh Manjit. The status of Government-funded radiotherapy centres in Nigeria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1111.
Abstract 3384: Evaluation of a tumor informed MRD assay with contrived breast cancer samples
Authors: Hugh Russell, Paul LaBrousse, Daniel Stetson, Greg Jones, Giovanni Marsico, Tim Forshew, Robert McEwen, Elza De Bruin, Christopher Abbosh, Darren Hodgson, Brian Dougherty, James Hadfield, Carl Barrett
Journal: Cancer Research (2023)

Abstract The non-invasive detection of circulating tumor DNA (ctDNA) from plasma has been shown to have clinical value for detection of minimal residual disease (MRD), emergence of resistance, and predicting treatment response. The sensitive detection of MRD following curative treatment allows for the identification of patients destined to recur. Higher assay sensitivities enable the longest lead times to clinical recurrence. Evaluations using several contrived pan-cancer samples have shown that the Inivata RaDaR tumor-informed personalized assay has a high sensitivity to detect ctDNA. The tumor-informed analysis utilizes sequencing of the tumor tissue to identify up to 48 clonal somatic variants, which are selected to generate a personalized panel to track the variants in patient plasma. To evaluate this technology in a disease specific manner, we generated a set of contrived plasma samples from commercial breast cancer patients and healthy individuals. The biological materials allowed us to generate a plasma sample with defined range of tumor content between 0.2 and 0.001% variant allele fraction (VAF). The sample dilutions were intended to recapitulate challenging cell-free DNA inputs that can be encountered in a clinical setting (median input: 5.76 ng [range 0.22 to 103.73]. Through our pan-cancer and breast cancer evaluations, we were able generate both sensitivity metrics along with a small limit of detection (LOD) study. The assay successfully detected tumor fractions in samples tested at 1X and 1.5X of the established LOD95% of 0.0011% VAF. RaDaR was able to detect the majority of MRD+ samples at 0.5X LOD. We will present data showing the level of sensitivity based on using both 2000 and 20000 genomic equivalents. The RaDaR assay showed high sensitivity for pan-cancer as well as ER+ breast cancer, which is known to have a low TMB compared to other subtypes. In this albeit small LoD study the Inivata assay was highly sensitive for the detection of ctDNA which is imperative to confidently detect ctDNA in advance of overt clinical recurrence. Citation Format: Hugh Russell, Paul LaBrousse, Daniel Stetson, Greg Jones, Giovanni Marsico, Tim Forshew, Robert McEwen, Elza De Bruin, Christopher Abbosh, Darren Hodgson, Brian Dougherty, James Hadfield, Carl Barrett. Evaluation of a tumor informed MRD assay with contrived breast cancer samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3384.
Abstract 6351: Reversal of dysfunctional CIK cells after the exposure to resistant cholangiocarcinoma cells through chemical perturbation of resistant gene signature
Authors: Adisak Wongkajornsilp, Khin Su Su Htwe, Porncheera Chusorn, Sunisa Duangsa-ard, Kanda Kasetsinsombat, Nathawadee Sawatpiboon
Journal: Cancer Research (2023)

Abstract Clinical trials on cholangiocarcinoma revealed differential sensitivity to cytolytic action of allogeneic cytokine-induced killer (CIK) cells. Different metastatic foci in the same individual could also display different sensitivity. The differential sensitivity of separate lines of cultured cholangiocarcinoma cells could be demonstrated based on the evaluation of GR50. Allogeneic CIK cell or CD3+CD56+ subset was co-cultured with nine cell lines at E:T ratio of 20:1 for 48 h. The tumor cells were categorized into 2 groups based on the obtained GR50. This resulted in 4 sensitive cell lines and 5 resistant cell lines. The cholangiocarcinoma cell-exposed CIK cell and CD3+CD56+ subset displayed defective anti-tumor cytotoxicity upon subsequent experiment. RNAseq analysis revealed 261 genes upregulated in sensitive cell lines and 665 genes upregulated in resistant cell lines. The top 50 resistant genes were evaluated for their linked signal transduction and protein interaction network. Based on the interaction network, a list of chemicals that could interrupt the stipulated network were selected. They were assayed for their synergistic activity with dysfunctional CIK cell or CD3+CD56+ subset for cytolysis of resistant tumor cells. Citation Format: Adisak Wongkajornsilp, Khin Su Su Htwe, Porncheera Chusorn, Sunisa Duangsa-ard, Kanda Kasetsinsombat, Nathawadee Sawatpiboon. Reversal of dysfunctional CIK cells after the exposure to resistant cholangiocarcinoma cells through chemical perturbation of resistant gene signature [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6351.
Abstract 3345: Tissue of origin (TOO) localization using targeted methylation biomarkers discovered by whole-genome bisulfite sequencing
Authors: Qiang Wei, Wanglong Deng, Zhihui Xu, Yihui Han, Yuan Yang, Chao Zhang, Xiaoqiang Wang, Xuan Tang, Chao Song, Qing Xu, Yong Ren
Journal: Cancer Research (2023)

Abstract DNA methylation is a promising biomarker for tissue of origin (TOO) localization, which is important for classification of cancer of unknown primary site (CUP) in multiple cancer early detection. The current most of CpG sites of TOO focused on CpG islands based on The Cancer Genome Atlas (TCGA) data sets, but remains largely under-explored across the whole genome. In this study, we conducted the whole-genome bisulfite sequencing (WGBS) in 481 tumor samples and 361 matched adjacent normal tissue samples for 9 common types of cancers, including lung, breast, colon, liver, stomach, lymph, pancreas, esophageal and ovarian. After adjusted the tumor cells’ DNA methylation rates, 3,000 CpG sites, 60% of which were not on CpG islands, were selected through Random Forest classifier (multi-class) to identify cancer type. To evaluate these TOO methylation biomarkers, we used Random Forest Model to predict TOO of the methylation data sets in The Cancer Genome Atlas (TCGA), including 1,704 tumor samples. The results showed that accuracy of TOO could achieve 98.5% for these tumor samples of TCGA. Among these samples, the accuracy of TOO of breast, liver, lung, colorectal and pancreas were 99.6%, 99.9%, 97.7%, 99.2% and 99.3% respectively. Several samples from Esophagus and Stomach were classified to each other, and their accuracy of TOO was relatively low, 97.6% and 96.7%. It demonstrated that these methylation biomarkers could detect multiple cancers, and the multi-class model had good performance for TOO localization. Citation Format: Qiang Wei, Wanglong Deng, Zhihui Xu, Yihui Han, Yuan Yang, Chao Zhang, Xiaoqiang Wang, Xuan Tang, Chao Song, Qing Xu, Yong Ren. Tissue of origin (TOO) localization using targeted methylation biomarkers discovered by whole-genome bisulfite sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3345.
Abstract 5396: Early detection of ovarian cancer using mRNA sample data to investigate the correlation of specific gene mutations with ovarian cancer
Authors: Zahra Saghaie, Christine Richardson, M. Taghi Mostafavi
Journal: Cancer Research (2023)

Abstract Introduction: Ovarian cancer (OC) is the second most common gynecologic cancer in the U.S, and is the deadliest cancer of the female reproductive system. Because of the complex nature of OC, diagnoses are often by display of symptoms at late stages of disease. Identifying OC at early stages can increase the 5-year survival rate from 40% in stage IV to 94% in stage I. Therefore, effective screening and detection of OC at early stages is imperative. The main objective of this study is to develop a diagnostic panel of markers that correlate with early-stage OC, and ultimately, improve the survival rate of patients. Background: Approaches in the past several years to detect malignant OC have focused on processing relevant images or screening genomic data. These studies use liquid-based biopsies, sonographic images, cyst images, CT images, MR imaging and genomics data. Some studies have focused on distinguishing malignant tumors versus benign tumor cells. In addition to statistical methods to examine available genomic datasets, Machine Learning models including K-Nearest Neighbor, K-means, Convolutional Neural Networks, Deep Learning, Support Vector Machine, Random Forest, and Fuzzy algorithms have been used. Methods: In this study we proposed a method to determine a possible correlation between some actively expressed genes and OC, using publicly available mRNA data sets. The samples were retrieved from the GSE106817 dataset via the NCBI GEO site, with 333 cancerous and 2759 Non-cancerous samples. The objective is to define a set of genes which is able to illustrate prediction of correlation through the use of PCA, NMF and SVD. We further verified our findings by testing on one additional different mRNA datasets. For this, we compared several machine learning algorithms to potentially correlate active genes and OC stages, from the available data. Results and Discussions: Through our study we have developed Machine Learning models valuable to identify patterns of disease at different stages, thus, potentially be useful in developing predictive models. Our initial experimental results have been demonstrated with a set of mRNA signatures, which may be used to create a panel of biomarkers valuable for detecting early-stage OC. Our results confirm the correlation between OC and PAX8, PEG3, and BIRC5, and MYB and RAC2. Continuation of this study highlights methods towards the early detection of OC and to improve disease identification outcome. Citation Format: Zahra Saghaie, Christine Richardson, M. Taghi Mostafavi. Early detection of ovarian cancer using mRNA sample data to investigate the correlation of specific gene mutations with ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5396.
Apollo: A randomized phase II double-blind study of olaparib versus placebo following curative intent therapy in patients with resected pancreatic cancer and a pathogenic <i>BRCA1</i>,<i> BRCA2</i>, or <i>PALB2</i> mutation—ECOG-ACRIN EA2192.
Authors: Kim Anna Reiss, Sung Chul Hong, Anup Kasi, Eileen Mary O'Reilly, Shishir K. Maithel, Xin Yao, Stanley R. Hamilton, Ben Boursi, Michael J. Pishvaian, Samuel J Klempner, Susan M. Domchek, Paul J. Catalano, E. Gabriela Chiorean, Philip Agop Philip, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2023)

TPS4202 Background: A meaningful subset of PDAC is characterized by a homologous recombination deficiency (HRD). The most well-defined patients within this group are those with pathogenic variants in BRCA1, BRCA2 and PALB2. In the metastatic setting, PARP inhibitor maintenance provides a progression-free survival benefit after a period of platinum based chemotherapy 1,2 , but the role of PARP inhibitors in the curative intent setting is undefined. The OlympiA study established one year of olaparib as the standard of care for patients with BRCA-related, early stage breast cancer who completed all other curative-intent treatment 3 . Therefore, we have designed a randomized, phase II double-blind study of one year of olaparib vs placebo in patients with pancreatic cancer and a germline or somatic variant in BRCA or PALB2 who have completed all curative intent therapy. Methods: We have enrolled and treated 29 of 152 planned patients on study NCT 04858334/EA2192. Eligibility criteria include: a pathogenic germline or somatic variant in BRCA1, BRCA2 or PALB2 as determined by local laboratory (central review required); completion of curative-intent resection and ≥ three months of multi-agent chemotherapy; no evidence of recurrent disease. At enrollment, patients must be within 12 weeks of their last anti-cancer intervention. Patients are randomized 2:1 to receive oral olaparib 300 mg twice daily or placebo for 12 28-day cycles. The primary endpoint is relapse-free survival. Overall survival is a secondary endpoint. Tumor tissue, fecal material (for microbiome analysis) and serial ctDNA samples are being collected. 1) Golan T, Locker GY, Kindler HL: Maintenance Olaparib for Metastatic Pancreatic Cancer. Reply. N Engl J Med 381:1492-1493, 2019. 2) Reiss KA, Mick R, O'Hara MH, et al: Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2. J Clin Oncol 39:2497-2505, 2021. 3) Tutt ANJ, Garber JE, Geyer CE, Jr.: Adjuvant Olaparib in BRCA-Mutated Breast Cancer. Reply. N Engl J Med 385:1440, 2021. Clinical trial information: NCT04858334 .
EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis
Authors: Alen Zabotti, Gabriele De Marco, Laure Gossec, Xenofon Baraliakos, Daniel Aletaha, Annamaria Iagnocco, Paolo Gisondi, Peter V Balint, Heidi Bertheussen, Wolf-Henning Boehncke, Nemanja S Damjanov, Maarten de Wit, Enzo Errichetti, Helena Marzo-Ortega, Mikhail Protopopov, Lluis Puig, Rubén Queiro, Piero Ruscitti, Laura Savage, Georg Schett, Stefan Siebert, Tanja A Stamm, Paul Studenic, Ilaria Tinazzi, Filip E Van den Bosch, Annette van der Helm-van Mil, Abdulla Watad, Josef S Smolen, Dennis G McGonagle
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. <h3>Objective</h3> To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. <h3>Methods</h3> A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. <h3>Results</h3> Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. <h3>Conclusion</h3> These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development.
Abstract 6309: Anti-tumor efficacy of SI-B001, a novel EGFR × HER3 bispecific antibody, against EGFR-driven epithelial tumors alone or in combination with paclitaxel and carboplatin
Authors: Blair Renshaw, Jahan Salar Khalili, Sa Xiao, Yi Zhu
Journal: Cancer Research (2023)

Abstract EGFR is a member of the human epidermal growth factor receptor (ErbB) family with tyrosine kinase activity. Evidence indicates that EGFR is involved in the pathogenesis and progression of human carcinoma of different types. HER3 is a unique pseudokinase receptor of the ErbB family and known to mediate resistance to EGFR-targeting therapies. Therefore, we created SI-B001, an EGFR × HER3 bispecific antibody, which can bind EGFR × EGFR homodimers and EGFR × HER3 heterodimer to block their downstream pathways. We performed non-clinical studies to investigate in vitro and in vivo anti-tumor effects. In vitro, the inhibition of tumor cell growth by SI-B001 was stronger than cetuximab and duligotuzumab in FaDu (mRNA expression levels of EGFRhigh/HER3high/NRG1medium). Importantly, testing with the cell line Oka-c-1 (mRNA expression levels of EGFRhigh/HER3high/NRG1low), showed that NRG1 supplementation did not change the potency of cetuximab. However, SI-B001 showed much stronger potency than cetuximab and duligotuzumab under conditions of NRG1 supplementation. This result indicates that the functionality of the bi-specific SI-B001 is competitive against a HER3 natural ligand and capable to act against cancer with HER3 ligand mediated resistance to cetuximab. In vivo, single agent SI-B001 exhibited superior anti-tumor activity to cetuximab in the FaDu xenograft model. Meanwhile, SI-B001 in combination with paclitaxel and carboplatin led to a significant synergistic antitumor effect, which was stronger than the combination of cetuximab + paclitaxel + carboplatin. Compared to chemotherapy alone in this model, which could result in weight loss and treatment related mortality, no serious weight loss or deaths occurred in the single agent SI-B001 and the combination of SI-B001 with chemotherapy. These results suggest that SI-B001 alone and in combination with chemotherapy can exhibit favorable safety and robust anti-tumor activity. Currently, 6 phase II clinical trials of SI-B001, either alone or in combination with chemotherapy, have been conducted in different epithelial carcinomas. These studies have shown a potential break-through activity in NSCLC and HNSCC with a very good safety profile. Citation Format: Blair Renshaw, Jahan Salar Khalili, Sa Xiao, Yi Zhu. Anti-tumor efficacy of SI-B001, a novel EGFR × HER3 bispecific antibody, against EGFR-driven epithelial tumors alone or in combination with paclitaxel and carboplatin. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6309.